.alpha.,.alpha.-Difluoro-.beta.-hydroxy thiol esters are useful as intermediates in organic syntheses of valuable pharmaceutical products.
A particularly useful .alpha.,.alpha.-difluoro-.beta.-hydroxy ester is: ##STR2## where R.sup.1 is selected from the group consisting of H, C.sub.1 -C.sub.4 alkyl, substituted alkyl, including silyl alkyl, trialkylsilyl, aryl, substituted aryl, including silyl aryl, R.sup.2 is independently selected from alkyl and aryl groups, and Q is either S (for thiol esters) or O (for esters). Compounds of formula I are known to be useful in the synthesis of gemcitabine hydrochloride (II), a known anti-neoplastic agent. ##STR3##
Existing methods to make compounds of formula I where R.sup.1 is SiR.sup.3 R.sup.4 R.sup.5, R.sup.2 is R.sup.6, Q is S, and R.sup.3, R.sup.4, R.sup.5 and R.sup.6 are independently selected from C.sub.1 -C.sub.4 alkyl and C.sub.5 -C.sub.6 aryl groups are known in the art. See U.S. Pat. No. 5,428,176. The processes to make compounds of formula (I) as described in the '176 patent require a trialkyl (or triaryl) silylhalide and the use of a catalyst.
Existing methods to make compounds of formula I where R.sup.1 is trialkylsilyl, R.sup.2 is alkyl and Q is O, are described and claimed in European Patent Application No. 94308806.2 (Publication No. 655454). These methods also require a trialkylsilyl halide and the use of a catalyst.
It is desirable to develop alternate processes that use fewer reagents to make certain .alpha.,.alpha.-difluoro-.beta.-hydroxy thiol esters, because the use of fewer reagents would lower the overall cost of the synthesis. It is also desirable to synthesize additional .alpha.,.alpha.-difluoro-.beta.-hydroxy thiol ester compounds which are useful as intermediates in organic syntheses of valuable pharmaceutical products.